Genetic Analysis of Disheveled 2 and Disheveled 3 in Human Neural Tube Defects

• DOI: 10.1007/s12031-012-9871-9
• Publication Date: 2012-08-14T18:02:54Z
• Authors: Patrizia De Marco; Elisa Merello; Alessandro Consales; Gianluca Piatelli; Armando Cama; Zoha Kibar; Valeria Capra
• Keywords: Male; 0303 health sciences; Genotype; Dishevelled Proteins; Intracellular Signaling Peptides and Proteins; Mutation, Missense; Cell Polarity; Membrane Proteins; Exons; Cadherins; Phosphoproteins; Article; Cellular and Molecular Neuroscience; Mutagenesis, Insertional; 03 medical and health sciences; Amino Acid Substitution; Codon, Nonsense; Ethnicity; Humans; Point Mutation; Female; Neural Tube Defects; Carrier Proteins; Adaptor Proteins, Signal Transducing

Neural tube defects are severe malformations affecting 1/1,000 live births. The planar cell polarity pathway controls the neural closure and has been implicated in pathogenesis of both animal models human cohorts. In mouse disruption Dvl2 alone (Dvl2 (-/-)) or Dvl3 (-/-); (+/-), (+/-); results incomplete neurulation, suggesting a role for Disheveled closure. is multifunctional protein that involved canonical Wnt signaling noncanonical pathway. this study, we analyzed orthologs DVL2 DVL3 cohort 473 patients with defects. Rare variants were genotyped 639 ethnically matched controls. We identified seven rare missense mutations absent all analyzed. Two these mutations, p.Tyr667Cys p.Ala53Val, predicted to be detrimental silico. Significantly, 1-bp insertion (c.1801_1802insG) exon 15 lead truncation was patient complex form caudal agenesis. summary, demonstrate possible gene as risk factors